Technetium-99m generator

The first technetium-99m generator, unshielded, 1958. A Tc-99m pertechnetate solution is being eluted from Mo-99 molybdate bound to a chromatographic substrate

A technetium-99m generator, or colloquially a technetium cow or moly cow, is a device used to extract the metastable isotope 99mTc of technetium from a source of decaying molybdenum-99. 99Mo has a half-life of 66 hours[1] and can be easily transported over long distances to hospitals where its decay product technetium-99m (with a half-life of only 6 hours, inconvenient for transport) is extracted and used for a variety of nuclear medicinediagnostic procedures, where its short half-life is very useful.

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99Mo can be obtained by the neutron activation (n,γ reaction) of 98Mo in a high neutron flux reactor. However, the most frequently used method is through fission of uranium-235 in a nuclear reactor. While most reactors currently engaged in 99Mo production use highly enriched uranium-235 targets, proliferation concerns have prompted some producers to transition to low enriched uranium targets[2] The target is irradiated with neutrons to form 99Mo as a fission product[1]. Molybdenum-99 is then separated from other fission products in a hot cell.[2]

Tc-99m remained a scientific curiosity until the 1950s when Powell Richards realized the potential of technetium-99m as a medical radiotracer and promoted its use among the medical community. While Richards was in charge of the radioisotope production at the Hot Lab Division of the Brookhaven National Laboratory, Walter Tucker and Margaret Greene were working on how to improve the separation process purity of the short-lived eluteddaughter productiodine-132 from tellurium-132, its 3.2-days parent, produced in the Brookhaven Graphite Research Reactor.[3] They detected a trace contaminant which proved to be Tc-99m, which was coming from Mo-99 and was following tellurium in the chemistry of the separation process for other fission products. Based on the similarities between the chemistry of the tellurium-iodine parent-daughter pair, Tucker and Greene developed the first technetium-99m generator in 1958 (see photo of this generator at the beginning of the article).[4][5] It was not until 1960 that Richards became the first to suggest the idea of using technetium as a medical tracer.[6][7][8][9]

Technetium-99m's short half-life of 6 hours makes storage impossible and would make transport very expensive. Instead its parent nuclide 99Mo is supplied to hospitals after its extraction from the neutron-irradiated uranium targets and its purification in dedicated processing facilities.[10] It is shipped by specialised radiopharmaceutical companies in the form of technetium-99m generators worldwide or directly distributed to the local market. The generators, colloquially known as a moly cows, are devices designed to provide radiation shielding for transport and to minimize the extraction work done at the medical facility. A typical dose rate at 1 metre from Tc-99m generator is 20-50 μSv/h during transport.[11] These generators' output declines with time and must be replaced weekly, since the half-life of 99Mo is still only 66 hours.

Since the half-life of the parent nuclide (99Mo) is much longer than that of the daughter nuclide (99mTc), 50% of equilibrium activity is reached within one daughter half-life, 75% within two daughter half-lives. Hence, removing the daughter nuclide (elution process) from the generator ("milking" the cow) is reasonably done as often as every 6 hours in a 99Mo/99mTc generator.

Most commercial 99Mo/99mTc generators use column chromatography, in which 99Mo in the form of molybdate, MoO42− is adsorbed onto acid alumina (Al2O3). When the Mo-99 decays it forms pertechnetate TcO4−, which, because of its single charge, is less tightly bound to the alumina. Pouring normal saline solution through the column of immobilized 99Mo elutes the soluble 99mTc, resulting in a saline solution containing the 99mTc as the pertechnetate, with sodium as the counterbalancing cation.

The solution of sodium pertechnetate may then be added in an appropriate concentration to the organ-specific pharmaceutical to be used, or sodium pertechnetate can be used directly without pharmaceutical tagging for specific procedures requiring only the 99mTcO4− as the primary radiopharmaceutical. A large percentage of the 99mTc generated by a 99Mo/99mTc generator is produced in the first 3 parent half-lives, or approximately one week. Hence, clinical nuclear medicine units purchase at least one such generator per week or order several in a staggered fashion.

When the generator is left unused, 99Mo decays to 99mTc, which in turn decays to 99Tc. The half-life of 99Tc is far longer than its metastable isomer, so the ratio of 99Tc to 99mTc increases over time. Both isomers are carried out by the elution process and react equally well with the ligand, but the 99Tc is an impurity useless to imaging.

The generator is washed of Tc-99 and Tc-99m at the end of the manufacturing process of the generator, but the ratio of 99Tc to 99mTc then builds up again during transport or any other period when the generator is left unused. The first few elutions will have reduced effectiveness because of this high ratio.[12]